Understanding cardiac safety early is critical in drug development. In their latest poster, Jazz Pharmaceuticals, explain how they utilised Metrion’s clinically translatable cardiotoxicity assay to do exactly that.
Lysosomes are a critical component of eukaryotic cells, playing a role in degradation and recycling processes, signal transduction and extracellular secretion(I). Ion channels expressed on the endo-lysosomal membrane are crucial in intracellular signalling and maintaining the acidic luminal pH for optimal hydrolase activity(II). There are a number metabolic disorders, known as lysosomal storage diseases, that arise from lysosomal dysfunction(III).
Furthermore, targeting the autophagic-lysosomal pathway is a novel therapeutic strategy for clearance of toxic aggregates, which are pathological hallmarks of many neurodegenerative diseases. Endo-lysosomal channels have been historically challenging to investigate due to their intracellular location in small-sized organelles. However, advances in lysosomal biology have developed a technique to enlarge and extract endo-lysosomes to be recorded using conventional patch-clamp methods.
We applied a refined manual patch-clamp technique to characterize endogenous endo-lysosomal ion channels in their native environment, suitable for investigating potential therapeutic agents. In the present study we focused on the activity of TRPML and TMEM175 channels, due to their respective implications in mucolipidosis type IV(IV) and Parkinson’s disease(II). Moreover, we investigated how pH differences found along the endocytic pathway can affect TRPML channel activation.
Understanding cardiac safety early is critical in drug development. In their latest poster, Jazz Pharmaceuticals, explain how they utilised Metrion’s clinically translatable cardiotoxicity assay to do exactly that.
Development of a robust hNaV1.9 high-throughput screening assay on the Sophion Qube384 platform. This is complemented by a suite of ion channel selectivity assays and sensory neuron recordings to create a versatile screening cascade to support NaV1.9 drug discovery programmes.